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Clinical role of N otch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas
Author(s) -
Ikemoto Tetsuya,
Sugimoto Koji,
Shimada Mitsuo,
Utsunomiya Tohru,
Morine Yuji,
Imura Satoru,
Arakawa Yusuke,
Kanamoto Mami,
Iwahashi Shuichi,
Saito Yu,
Yamada Shinichiro
Publication year - 2015
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12660
Subject(s) - medicine , pancreas , pathology , intraductal papillary mucinous neoplasm , immunohistochemistry , population , staining , gastroenterology , cancer research , environmental health
Background and Aim This study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms ( IPMN s). It is incontrovertible that regulatory T cells ( T regs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral T regs remains unclear. It is also known that the N otch signaling pathway is involved in T reg suppressor function. Moreover, IPMN s have a high malignant potential. Methods Peripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN . Resected specimens were immunohistochemically evaluated (anti‐ N otch1, anti‐ N otch2, and anti‐ N otch2‐intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral T reg populations were analyzed with an automated flow cytometer. Results Disease‐free survival was significantly worse in the N otch1 high‐expression group ( P = 0.023). N otch2 family expressions were higher in intraductal papillary mucinous carcinoma ( IPMC ) than in intraductal papillary mucinous adenoma ( IPMA ) ( N otch2, P = 0.012; N otch2‐intracellular domain, P = 0.036). J agged1 expression was significantly higher in IPMC than in IPMA ( P < 0.05) and was significantly related to recurrence. The T reg population in peripheral blood was higher in patients with IPMC than in those with IPMA ( P < 0.01). Conclusions N otch signaling, especially J agged1 expression, reflects IPMN aggressiveness. Our data may suggest that the N otch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral T reg population.